[unreadable] Non-alcoholic steatohepatitis (NASH) is increasingly recognized as a common form of chronic liver disease in the United States. NASH is characterized by distinct histological features that include steatosis, ballooning degeneration, lobular inflammation and varying degrees of fibrosis. It is commonly associated with the metabolic syndrome, the incidence of which is rising in the U.S. Patients with NASH are at risk of progression to cirrhosis and ultimately to hepatocellular carcinoma and premature death. There is no standard therapy for management of NASH at this point. Several approaches to drug therapy have been evaluated in small clinical trials for the treatment of NAFLD in humans and in animals but most studies have been inconclusive with uncertain benefits because of small sample size, lack of placebo, lack of follow-up liver biopsies and/or inadequate follow-up to evaluate treatment benefit. Studies that identify the pathogenesis of liver injury, predictors of aggressive forms of the disease as well as well designed studies that will show efficacy of medical interventions aimed at improving steatosis and inflammation and slowing down progression of disease will be major contributions for this growing health-problem. We propose a randomized, double-blind, placebo controlled study of a fibric acid derivative 'fenofibrate', a PPARa agonist with potent effects in decreasing hepatic steatosis and inflammation for treatment of patients with histologically proven NASH. We hypothesize that fenofibrate treatment will lead to a significant improvement in steatosis and inflammation and improve insulin sensitivity in patients with NASH. Our specific aims are: (1) To assess the degree of histological improvement of NASH as defined by > 2 point decrease in global NASH score using the NASH-CRN scoring system in patients undergoing treatment with fenofibrate, (2) To assess the effect of fenofibrate in improving insulin sensitivity in patients with NASH and (3) To assess the effect of fenofibrate on PPAR gene expression and fatty acid metabolism in liver tissue of patients with NASH. To our knowledge, this is the first randomized, placebo-controlled study of a PPARa agonist in humans with NASH. The planned gene expression analysis in liver tissue of patients with NASH will provide, for the first time, a snapshot of the action of these drugs to change hepatic gene expression in humans. We believe that the proposed studies will be an important contribution to our understanding not only of the pathogenesis of NASH, but will provide additional insights into treatment options for this very important disease [unreadable] [unreadable]